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Josephson junctions are typically characterized by a single phase difference across two superconductors. This conventional two-terminal Josephson junction can be generalized to a multiterminal device where the Josephson energy contains terms with contributions from multiple independent phase variables. Such multiterminal Josephson junctions (MTJJs) are being considered as platforms for engineering effective Hamiltonians with nontrivial topologies, such as Weyl crossings and higher-order Chern numbers. These prospects rely on the ability to create MTJJs with nonclassical multiterminal couplings in which only a few quantum modes are populated. Here, we demonstrate these requirements in a three-terminal Josephson junction fabricated on selective-area-grown (SAG) PbTe nanowires. We observe signatures of a π-shifted Josephson effect, consistent with interterminal couplings mediated by four-particle quantum states called Cooper quartets. We further observe a supercurrent coexistent with a non-monotonic evolution of the conductance with gate voltage, indicating transport mediated by a few quantum modes in both two- and three-terminal devices.
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Semiconductor nanowire (NW) quantum devices offer a promising path for the pursuit and investigation of topologically-protected quantum states, and superconducting and spin-based qubits that can be controlled using electric fields. Theoretical investigations into the impact of disorder on the attainment of dependable topological states in semiconducting nanowires with large spin-orbit coupling andg-factor highlight the critical need for improvements in both growth processes and nanofabrication techniques. In this work, we used a hybrid lithography tool for both the high-resolution thermal scanning probe lithography and high-throughput direct laser writing of quantum devices based on thin InSb nanowires with contact spacing of 200 nm. Electrical characterization demonstrates quasi-ballistic transport. The methodology outlined in this study has the potential to reduce the impact of disorder caused by fabrication processes in quantum devices based on 1D semiconductors.
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A paper by the current authors Paul and Nelson [JASA Express Lett. 3(9), 094802 (2023)] showed how the singular value decomposition (SVD) of the matrix of real weights in a neural network could be used to prune the network during training. The paper presented here shows that a similar approach can be used to reduce the training time and increase the implementation efficiency of complex-valued neural networks. Such networks have potential advantages compared to their real-valued counterparts, especially when the complex representation of the data is important, which is the often case in acoustic signal processing. In comparing the performance of networks having both real and complex elements, it is demonstrated that there are some advantages to the use of complex networks in the cases considered. The paper includes a derivation of the backpropagation algorithm, in matrix form, for training a complex-valued multilayer perceptron with an arbitrary number of layers. The matrix-based analysis enables the application of the SVD to the complex weight matrices in the network. The SVD-based pruning technique is applied to the problem of the classification of transient acoustic signals. It is shown how training times can be reduced, and implementation efficiency increased, while ensuring that such signals can be classified with remarkable accuracy.
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KEY POINTS: The developmental changes of the caval (SVC) and pulmonary vein (PV) myocardium electrophysiology are traced throughout postnatal ontogenesis. The myocardium in SVC as well as in PV demonstrate age-dependent differences in the ability to maintain resting membrane potential, to manifest automaticity in a form of ectopic action potentials in basal condition and in responses to the adrenergic stimulation. Electrophysiological characteristics of two distinct types of thoracic vein myocardium change in an opposite manner during early postnatal ontogenesis with increased proarrhythmicity of pulmonary and decreased automaticity in caval veins. Predisposition of PV cardiac tissue to proarrhythmycity develops during ontogenesis in time correlation with the establishment of sympathetic innervation of the tissue. The electrophysiological properties of caval vein cardiac tissue shift from a pacemaker-like phenotype to atrial phenotype in accompaniment with sympathetic nerve growth and adrenergic receptor expression changes. ABSTRACT: The thoracic vein myocardium is considered as a main source for atrial fibrillation initiation due to its high susceptibility to ectopic activity. The mechanism by which and when pulmonary (PV) and superior vena cava (SVC) became proarrhythmic during postnatal ontogenesis is still unknown. In this study, we traced postnatal changes of electrophysiology in a correlation with the sympathetic innervation and adrenergic receptor distribution to reveal developmental differences in proarrhythmicity occurrence in PV and SVC myocardium. A standard microelectrode technique was used to assess the changes in ability to maintain resting membrane potential (RMP), generate spontaneous action potentials (SAP) and adrenergically induced ectopy in multicellular SVC and PV preparations of rats of different postnatal ages. Immunofluorescence imaging was used to trace postnatal changes in sympathetic innervation, ß1- and α1A-adrenergic receptor (AR) distribution. We revealed that the ability to generate SAP and susceptibility to adrenergic stimulation changes during postnatal ontogenesis in an opposite manner in PV and SVC myocardium. While SAP occurrence decreases with age in SVC myocardium, it significantly increases in PV cardiac tissue. PV myocardium starts to demonstrate RMP instability and proarrhythmic activity from the 14th day of postnatal life which correlates with the appearance of the sympathetic innervation of the thoracic veins. In addition, postnatal attenuation of SVC myocardium automaticity occurs concomitantly with sympathetic innervation establishment and increase in ß1-ARs, but not α1A-AR levels. Our results support the contention that SVC and PV myocardium electrophysiology change during postnatal development, resulting in higher PV proarrhythmicity in adults.
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Fibrilación Atrial , Venas Pulmonares , Animales , Catecolaminas , Atrios Cardíacos , Miocardio , Ratas , Vena Cava SuperiorRESUMEN
Neural networks are increasingly being applied to problems in acoustics and audio signal processing. Large audio datasets are being generated for use in training machine learning algorithms, and the reduction of training times is of increasing relevance. The work presented here begins by reformulating the analysis of the classical multilayer perceptron to show the explicit dependence of network parameters on the properties of the weight matrices in the network. This analysis then allows the application of the singular value decomposition (SVD) to the weight matrices. An algorithm is presented that makes use of regular applications of the SVD to progressively reduce the dimensionality of the network. This results in significant reductions in network training times of up to 50% with very little or no loss in accuracy. The use of the algorithm is demonstrated by applying it to a number of acoustical classification problems that help quantify the extent to which closely related spectra can be distinguished by machine learning.
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Signatures of Majorana zero modes (MZMs) have been observed in semiconductor nanowires (NWs) with a strong spin-orbital interaction (SOI) with proximity-induced superconductivity. Realizing topological superconductivity and MZMs in this platform requires eliminating spin degeneracy by applying a magnetic field. However, the field can adversely impact the induced superconductivity and places geometric restrictions on the device. These challenges could be circumvented by integrating magnetic elements with the NWs. Here, we report the first experimental investigation of spin transport across InSb NWs with ferromagnetic (FM) contacts. We observe signatures of spin polarization and spin-dependent transport in the quasi-one-dimensional ballistic regime. Moreover, we show that electrostatic gating tunes the observed magnetic signal and reveals a regime where the device acts as a spin filter. These results open an avenue toward developing MZM devices with spin degeneracy lifted locally without external fields. They could also enable spin-based devices that leverage spin-orbital states in quantum wires.
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INTRODUCTION: The published data showed the importance of metabolic control in preventing complications in metabolic syndrome (MS) and the role of nutritional medical therapy in glycemic control and in the control of dyslipidemia, hypertension, weight loss/normalization (in overweight or malnourished subjects). OBJECTIVES: This study follows the evolution of sarcopenic index (SI) and other clinical parameters (body mass index (BMI), homeostasis evaluation index (HOMA index)) correlated with MS after diet therapy or diet therapy combined with sports, in patients with MS. PATIENTS AND METHODS: Our research was conducted during 12 months, on 110 patients >18 years of age, with HOMA index>2, divided into three groups: control group (CG, N=20), diet therapy group (DTG, N=58), diet therapy and sports group (DTSG, N=32). HOMA index for insulin resistance was calculated as the product of resting plasma insulin (in microunits/milliliter) and plasma glucose (in millimoles/liter), divided by 22.5. SI was determined using BIA, as being the ratio between muscle mass and fat mass, measured in cm2/m2. RESULTS: A significant decrease of BMI (p<0.05) in DTG (from 31.63 to 24.50) and DTSG (from 30.18 to 24.17) vs. CG was observed (Pearson coefficient r=0.281, p<0.001). Weight status changed significantly (p<0.05) in the high-risk patients. There was a significant decrease of HOMA index (p<0.05) in DTG (from 5.93 to 2.57), DTSG (from 3.93 to 2.23), and in CG an increase was observed (from 3.15 to 3.37). CONCLUSION: The best results in the prevention/ treatment of sarcopenia in MS patients were obtained for DTSG, which benefited from both the positive effect of diet and physical activity.
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The electrophysiological properties of the superior vena cava (SVC) myocardium, which is considered a minor source of atrial arrhythmias, were studied in this study during postnatal development. Conduction properties were investigated in spontaneously active and electrically paced SVC preparations obtained from 7-60-day-old male Wistar rats using optical mapping and microelectrode techniques. The presence of high-conductance connexin 43 (Cx43) was evaluated in SVC cross-sections using immunofluorescence. It was found that SVC myocardium is excitable, electrically coupled with the atrial tissue, and conducts excitation waves at all stages of postnatal development. However, the conduction velocity (CV) of excitation and action potential (AP) upstroke velocity in SVC were significantly lower in neonatal than in adult animals and increased with postnatal maturation. Connexins Cx43 were identified in both neonatal and adult rat SVC myocardium; however, the abundance of Cx43 was significantly less in neonates. The gap junction uncoupler octanol affected conduction more profound in the neonatal than in adult SVC. We demonstrated for the first time that the conduction characteristics of SVC myocardium change from a slow-conduction (nodal) to a high-conduction (working) phenotype during postnatal ontogenesis. An age-related CV increase may occur due to changes of AP characteristics, electrical coupling, and Cx43 presence in SVC cardiomyocyte membranes. Observed changes may contribute to the low proarrhythmicity of adult caval vein cardiac tissue, while pre- or postnatal developmental abnormalities that delay the establishment of the working conduction phenotype may facilitate SVC proarrhythmia.
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Sistema de Conducción Cardíaco/fisiología , Miocardio/patología , Vena Cava Superior/fisiología , Potenciales de Acción/fisiología , Animales , Fibrilación Atrial/metabolismo , Fibrilación Atrial/fisiopatología , Ontologías Biológicas , Conexina 43/metabolismo , Femenino , Uniones Comunicantes/metabolismo , Uniones Comunicantes/fisiología , Atrios Cardíacos/metabolismo , Sistema de Conducción Cardíaco/metabolismo , Masculino , Miocardio/metabolismo , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/fisiología , Ratas , Ratas Wistar , Vena Cava Superior/metabolismoRESUMEN
Extracellular ATP and nicotinamide adenine dinucleotide (ß-NAD) demonstrate properties of neurotransmitters and neuromodulators in peripheral and central nervous system. It has been shown previously that ATP and ß-NAD affect cardiac functioning in adult mammals. Nevertheless, the modulation of cardiac activity by purine compounds in the early postnatal development is still not elucidated. Also, the potential influence of ATP and ß-NAD on cholinergic neurotransmission in the heart has not been investigated previously. Age-dependence of electrophysiological effects produced by extracellular ATP and ß-NAD was studied in the rat myocardium using sharp microelectrode technique. ATP and ß-NAD could affect ventricular and supraventricular myocardium independent from autonomic influences. Both purines induced reduction of action potentials (APs) duration in tissue preparations of atrial, ventricular myocardium, and myocardial sleeves of pulmonary veins from early postnatal rats similarly to myocardium of adult animals. Both purine compounds demonstrated weak age-dependence of the effect. We have estimated the ability of ATP and ß-NAD to alter cholinergic effects in the heart. Both purines suppressed inhibitory effects produced by stimulation of intracardiac parasympathetic nerve in right atria from adult animals, but not in preparations from neonates. Also, ATP and ß-NAD suppressed rest and evoked release of acetylcholine (ACh) in adult animals. ß-NAD suppressed effects of parasympathetic stimulation and ACh release stronger than ATP. In conclusion, ATP and ß-NAD control the heart at the postsynaptic and presynaptic levels via affecting the cardiac myocytes APs and ACh release. Postsynaptic and presynaptic effects of purines may be antagonistic and the latter demonstrates age-dependence.
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Potenciales de Acción/efectos de los fármacos , Adenosina Trifosfato/farmacología , Corazón/efectos de los fármacos , Miocardio/metabolismo , NAD/farmacología , Potenciales de Acción/fisiología , Animales , Femenino , Masculino , Ratas , Ratas Wistar , Transmisión Sináptica/fisiologíaRESUMEN
We built a two-mirror based X-ray split and delay (XRSD) device for soft X-rays at the Linac Coherent Light Source free electron laser facility. The instrument is based on an edge-polished mirror design covering an energy range of 250 eV-1800 eV and producing a delay between the two split pulses variable up to 400 femtoseconds with a sub-100 attosecond resolution. We present experimental and simulation results regarding molecular dissociation dynamics in CH3I and CO probed by the XRSD device. We observed ion kinetic energy and branching ratio dependence on the delay times which were reliably produced by the XRSD instrument.
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Through systematic control of the Nd concentration, we show that the carrier density of the two-dimensional electron gas (2DEG) in SrTiO_{3}/NdTiO_{3}/SrTiO_{3}(001) can be modulated over a wide range. We also demonstrate that the NdTiO_{3} in heterojunctions without a SrTiO_{3} cap is degraded by oxygen absorption from air, resulting in the immobilization of donor electrons that could otherwise contribute to the 2DEG. This system is, thus, an ideal model to understand and control the insulator-to-metal transition in a 2DEG based on both environmental conditions and film-growth processing parameters.
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UvrB has a central role in the highly conserved UvrABC pathway functioning not only as a damage recognition element but also as an essential component of the lesion tracking machinery. While it has been recently confirmed that the tracking assembly comprises a UvrA2B2 heterotetramer, the configurations of the damage engagement and UvrB-DNA handover complexes remain obscure. Here, we present the first crystal structure of a UvrB dimer whose biological significance has been verified using both chemical cross-linking and electron paramagnetic resonance spectroscopy. We demonstrate that this dimeric species stably associates with UvrA and forms a UvrA2B2-DNA complex. Our studies also illustrate how signals are transduced between the ATP and DNA binding sites to generate the helicase activity pivotal to handover and formation of the UvrB2-DNA complex, providing key insights into the configurations of these important repair intermediates.
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Proteínas Bacterianas/química , ADN Helicasas/química , Proteínas de Unión al ADN/química , ADN/química , Adenosina Trifosfato/química , Proteínas Bacterianas/genética , Proteínas Bacterianas/metabolismo , Sitios de Unión , Cristalografía , Daño del ADN , ADN Helicasas/genética , ADN Helicasas/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Dimerización , Modelos Moleculares , Mutagénesis Sitio-Dirigida , Estructura Terciaria de ProteínaRESUMEN
INTRODUCTION: Prostate cancer is the second most common cancer, following lung cancer, and the fifth leading cause of cancer death in men worldwide. The onset of the disease, characterized by symptoms or changes caused by distant metastases, is rare and poses a challenge for clinicians and pathologists. We aimed to present a series of prostate carcinoma (PC) with unusual, histologically confirmed distant metastases (pM1) at the time of diagnosis, which raised suspicions of other types or origins of the primary tumor. MATERIALS AND METHODS: Patients diagnosed with PC and distant metastases within a five-year timeframe (2017-2022) were extracted from the hospital database. The following data were collected: patient's age, imaging data, serum PSA level, and histopathological evaluation results. Patients with unusual distant metastases were selected and analyzed. RESULTS: We identified 10 patients in whom the diagnosis of PC was established following histopathological examination of tissue taken from distant metastatic sites (pM1). In three patients, the location of distant metastases was unusual: retroperitoneal, cranial/dural/epicranial and supradiaphragmatic lymph nodes which posed diagnostic challenges. Establishing the prostate origin of the tumor relied on immunohistochemical (IHC) investigation guided by clinical-imaging information. CONCLUSIONS: A metastasis of PC may rarely present as a cranial/dural tumor, retroperitoneal, or supradiaphragmatic lymphadenopathies in a man over the age of 50, but it should be taken into consideration. In the absence of correlated clinical, imaging, and histopathological/IHC data, diagnosing distant metastasis from PC is difficult, especially considering its potentially confusing IHC profile.
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A previous paper by Paul and Nelson [(2021). J. Acoust. Soc. Am. 149(6), 4119-4133] presented the application of the singular value decomposition (SVD) to the weight matrices of multilayer perceptron (MLP) networks as a pruning strategy to remove weight parameters. This work builds on the previous technique and presents a method of reducing the size of a hidden layer by applying a similar SVD algorithm. Results show that by reducing the neurons in the hidden layer, a significant amount of training time is saved compared to the algorithm presented in the previous paper while no or little accuracy is being lost compared to the original MLP model.
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The phenomenon of non-reciprocal critical current in a Josephson device, termed the Josephson diode effect, has garnered much recent interest. Realization of the diode effect requires inversion symmetry breaking, typically obtained by spin-orbit interactions. Here we report observation of the Josephson diode effect in a three-terminal Josephson device based upon an InAs quantum well two-dimensional electron gas proximitized by an epitaxial aluminum superconducting layer. We demonstrate that the diode efficiency in our devices can be tuned by a small out-of-plane magnetic field or by electrostatic gating. We show that the Josephson diode effect in these devices is a consequence of the artificial realization of a current-phase relation that contains higher harmonics. We also show nonlinear DC intermodulation and simultaneous two-signal rectification, enabled by the multi-terminal nature of the devices. Furthermore, we show that the diode effect is an inherent property of multi-terminal Josephson devices, establishing an immediately scalable approach by which potential applications of the Josephson diode effect can be realized, agnostic to the underlying material platform. These Josephson devices may also serve as gate-tunable building blocks in designing topologically protected qubits.
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The Andreev bound state spectra of multi-terminal Josephson junctions form an artificial band structure, which is predicted to host tunable topological phases under certain conditions. However, the number of conductance modes between the terminals of a multi-terminal Josephson junction must be few in order for this spectrum to be experimentally accessible. In this work, we employ a quantum point contact geometry in three-terminal Josephson devices to demonstrate independent control of conductance modes between each pair of terminals and access to the single-mode regime coexistent with the presence of superconducting coupling. These results establish a full platform on which to realize tunable Andreev bound state spectra in multi-terminal Josephson junctions.
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The study of subtle effects on transport in semiconductors requires high-quality epitaxial structures with low defect density. Using hybrid molecular beam epitaxy (MBE), SrTiO3 films with a low-temperature mobility exceeding 42,000 cm2 V-1 s-1 at a low carrier density of 3 × 1017 cm-3 were achieved. A sudden and sharp decrease in residual resistivity accompanied by an enhancement in the superconducting transition temperature were observed across the second Lifshitz transition where the third band becomes occupied, revealing dominant intraband scattering. These films further revealed an anomalous behavior in the Hall carrier density as a consequence of the antiferrodistortive (AFD) transition and the temperature dependence of the Hall scattering factor. Using hybrid MBE growth, phenomenological modeling, temperature-dependent transport measurements, and scanning superconducting quantum interference device imaging, we provide critical insights into the important role of inter- versus intraband scattering and of AFD domain walls on normal-state and superconducting properties of SrTiO3.
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An often-overlooked side of the population aging process and the steady rise of non-communicable diseases reflects the emergence of novel infectious pathogens on the background of an altered host immune response. The aim of this article was to present the first record of a ciliate and flagellate protozoa recovered from the urine of an elderly patient and to review the existing medical literature involving these parasites. A 70-year-old female patient was admitted for breathing difficulties on the basis of an acute exacerbation of COPD (Chronic obstructive pulmonary disease) with respiratory insufficiency. The patient reported a long history of multiple comorbidities including COPD Gold II, chronic respiratory insufficiency, chronic heart failure NYHA III (New York Heart Association Functional Classification), type 2 diabetes and morbid obesity. During routine examinations, we ascertained the presence of two unusual protozoa, a ciliate and a flagellate, in the patient's urine samples, identified on morphological criteria to be most likely Colpoda spp. and Colpodella spp., with similarities to C. steinii and C. gonderi. The presence of these parasites was not associated with any clinical signs of urinary disease. Following a combined treatment with ceftriaxone and metronidazole, we observed the disappearance of these pathogens upon discharge from the primary care clinic. This study highlights the importance of including unusual pathogens in the differential diagnosis of cases which involve immunosuppression.
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Y-family DNA polymerase κ (Pol κ) can replicate damaged DNA templates to rescue stalled replication forks. Access of Pol κ to DNA damage sites is facilitated by its interaction with the processivity clamp PCNA and is regulated by PCNA mono-ubiquitylation. Here, we present cryo-EM reconstructions of human Pol κ bound to DNA, an incoming nucleotide, and wild type or mono-ubiquitylated PCNA (Ub-PCNA). In both reconstructions, the internal PIP-box adjacent to the Pol κ Polymerase-Associated Domain (PAD) docks the catalytic core to one PCNA protomer in an angled orientation, bending the DNA exiting the Pol κ active site through PCNA, while Pol κ C-terminal domain containing two Ubiquitin Binding Zinc Fingers (UBZs) is invisible, in agreement with disorder predictions. The ubiquitin moieties are partly flexible and extend radially away from PCNA, with the ubiquitin at the Pol κ-bound protomer appearing more rigid. Activity assays suggest that, when the internal PIP-box interaction is lost, Pol κ is retained on DNA by a secondary interaction between the UBZs and the ubiquitins flexibly conjugated to PCNA. Our data provide a structural basis for the recruitment of a Y-family TLS polymerase to sites of DNA damage.
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ADN Polimerasa Dirigida por ADN/química , ADN Polimerasa Dirigida por ADN/metabolismo , ADN/química , ADN/metabolismo , Antígeno Nuclear de Célula en Proliferación/química , Antígeno Nuclear de Célula en Proliferación/metabolismo , Microscopía por Crioelectrón , ADN/genética , Daño del ADN , ADN Polimerasa Dirigida por ADN/genética , Humanos , Antígeno Nuclear de Célula en Proliferación/genética , Unión Proteica , Ubiquitina/metabolismo , UbiquitinaciónRESUMEN
A lot of animal models are developed with aim to advance in atrial fibrillation (AF) understanding. The hybrid B6CBAF1 mice are used extensively as a background to create manifestation of various diseases, however, their atrial electrophysiology, autonomic sympathetic innervation of the heart and potential for AF investigation is poorly characterized. In the present study we used ECG and microelectrode recordings from multicellular atrial preparations to reveal attributes of atrial electrical activity in B6CBAF1. Also, experiments with a fluorescent false monoamine neurotransmitter and glyoxylic acid-based staining were carried out to characterize functionally and morphologically catecholaminergic innervation of the B6CBAF1 atria. Atrial myocardium of B6CBAF1 is highly prone to ectopic automaticity and exhibits abnormal spontaneous action potential accompanied by multiple postdepolarizations that result in proarrhythmic triggered activity unlike two parental C57Bl/6 and CBA strains. In vivo experiments revealed that B6CBAF1 hybrids are more susceptible to the norepinephrine induced AF. Also, sympathetic nerve terminals are partially dysfunctional in B6CBAF1 revealing lower ability to accumulate and release neurotransmitters unlike two parental strains. The analysis of the heart rate variability revealed suppressed sympathetic component of the autonomic heart control in B6CBAF1. The organization of sympathetic innervation is very similar morphologically in all three murine strains however the abundance of non-bifurcated catecholamine-positive fibers in B6CBAF1 was increased. These results suggest that B6CBAF1 mice exhibit enhanced intrinsic atrial proarrhythmicity, while the abnormalities of sympathetic neurotransmitter cycling probably underlie disturbed autonomic heart control.